The shear stress of flowing blood on arterial walls plays an important role in cardiovascular homeostasis, influencing a broad spectrum of processes including: the coagulation of blood and formation of thrombi, the adhesion of blood cells to surfaces, the production of vasoactive chemicals by endothelial cells, the turnover rate of endothelial cells, and the permeability of artery walls to macromolecules. Many of these processes are believed to play a role in the localization of atherosclerotic plaques in curved and branched arteries and the development of intimal hyperplasia in the anastomotic region of vascular grafts. In spite of the importance of wall shear stress in cardiovascular function, its magnitude and distribution in the circulation are not well known at present because of difficulties associated with direct in vivo measurement. Thus the broad objectives of the proposed research are to determine the distribution and magnitude of wall shear stress in the cardiovascular system; the physical factors which are most influential in the determination (e.g., geometry, fluid rheology, wall mechanics, systemic impedance ...); and the possibilities for manipulation of wall shear stress through vasoactive drugs. The research design involves close interaction among in vivo and in vitro experiments and computer simulations. In the proposed research the following studies will be conducted: 1. Wall shear rate will be measured in the thoracic aorta and the aortic arch of dogs under normal and drug-altered hemodynamic conditions. Flush mounted hot film anemometry will be used for the measurements. 2. Wall shear stress and associated velocity profiles will be measured in elastic (moving wall) models of curved and branched arteries and vascular graft anastomoses using Newtonian and non-Newtonian blood analog fluids. The photochromic method, a non-disturbing flow visualization technique, will be used for measurement of velocity profiles from which wall shear rates will be calculated. 3. Computer simulations of velocity fields and wall shear stress distributions in atherogenic curved and branched artery models taking into account realistic fluid rheology and wall mechanics will be developed. Finite difference schemes developed in collaboration with computational fluid dynamicists at NASA-Ames will be applied to realistic physiological flow simulations.